Experiences in Prophylactic and Ther¬ 
apeutic Immunization Against 
Tuberculosis. 

WITH SPECIAL REFERENCE TO SENATE 
RESOLUTION, NO. 89 , AND TO THE CON¬ 
DUCT OF THE INVESTIGATION ORDERED 
THEREIN. 


By DR. KARL VON RUOK, 
ASHEVILLE, N. C. 




























if 










** T I 






9 

J i 







A 




V 



* '* ' J . ■ ' 





H ‘ 





■ 







J 








J 


> 


\ 


Experiences in Prophylactic andTher 
apeutic Immunization Against 
Tuberculosis. 


WITH SPECIAL REFERENCE TO SENATE 
RESOLUTION, NO. 89 , AND TO THE CON¬ 
DUCT OF THE INVESTIGATION ORDERED 
THEREIN. . 



By DR. KARL VON RUCK, 

*» 

ASHEVILLE, N. C. 




\ 





At the International Tuberculosis Congress in Washing¬ 
ton, 1908, Prof. Irving Fisher, of Yale, presented statistical 
data on tuberculosis, according to which it was estimated 
that, in 1906, a total of 138,000 persons died of tuberculosis 
in the United States, and that 5,000,000 of all persons then 
living in our country will die of the disease. 

The economic loss to the nation from deaths due to tuber¬ 
culosis is over $8,000 per death, and the total in the United 
States exceeds the sum of $1,100,000,000 per annum. 

Translated in figures of dollars and cents, the seriousness 
of tuberculosis as a disease of the masses and as the most 
frequent disease in civilized countries, is staggering. In 
the United States alone, the Crusade against Tuberculosis 
expended during the year 1912, the sum of $20,000,000, and 
similar sums are spent annually in the effort to delimit the 
ravages of the Great White Plague. 

If Dr. von Ruck is confirmed in his claim that his vaccine 
will actually prevent tuberculosis and consumption, as 
Jennerisation prevents smallpox, it follows that the general 
adoption of his method will solve the tuberculosis problem 
in a single generation. 



<jf»oaw) ' 

DEC 22 W4 




INTRODUCTION. 


—<— 

In this communication I have attempted to bring out the 
following facts: 

1. The investigation of my tuberculosis remedies, under¬ 
taken by the Public Health Service under Senate Resolution 
No. 89, was ordered at my own solicitation and not because 
any doubt existed as to my good faith or ability. 

2. In an investigation of this kind, I had a right to expect 
to be consulted regarding my views on the scope and the mode 
of proceedings. There was no good reason why the officers 
detailed for the work in Asheville should have acted under 
secret orders, and no reason why I should not have been per¬ 
mitted to take cognizance of their work in all its details. 

3. When the officers refused to consider the practical appli¬ 
cation of my method, and insisted on limiting their investi¬ 
gation to the animal experiment, my objections to this one¬ 
sided proceeding were entitled to consideration. 

4. The insistence of the Hygienic Laboratory on under¬ 
taking experiments with a preparation of the vaccine which 
I had refused to endorse fully, for reasons clearly stated, 
and the whole tacfics of the officers of the Public Health 
Service strongly suggest an animus on their part and a desire 
to disprove my work at all costs. 

5. Since it is not likely that I should have sought an 
official investigation of my work, if I had not been perfectly 
certain of my ground, and since it is unthinkable that, having 
sought the investigation, I would do anything to hamper or 
impede it, provided it was conducted fairly, it was in bad 
taste to treat me and my assistants as though we were on 
trial for our veracity and integrity. 

6. The preventive vaccination against tuberculosis, which 
I claim to have proved to be possible, is of such great im¬ 
portance for the welfare of the nation and of all mankind, 
that its verification or disproval can not be left to a preju¬ 
diced and arbitrary investigation. I demand the right to 
submit my proofs to a tribunal which I can accept as capable 
of deciding the question and as unbiased by personal con¬ 
siderations, so that the guarantee is afforded that the work, 
which I have already accomplished, shall be judged on its 
merits. 


4 



LANCET CLINIC PRESS 
CINCINNATI 


M Y tuberculosis studies which had for their object the dis¬ 
covery and perfection of a method of prophylactic vac¬ 
cination against the disease, had been pursued for a number of 
years prior to my publication in the Journal of the American 
Association (1912, LYIII, 1504), in which I announced uni¬ 
form success in the animal experiment and supplied every 
possible clinical and experimental basis to justify the prac¬ 
tical adoption of the method there described. It appeared safe, 
simple and efficient in the administration of a single dose, 
not only in my own, hands but in those of other physicians, 
and the remarkable changes for the better, in children al¬ 
ready the subjects of tuberculous infection, as described in 
the series of cases reported by Dr. Julian (Medical Record, 
1913, LXXXIII, 1059), justified the expectation that the 
vaccine would likewise prove strikingly efficient in the treat¬ 
ment of tuberculosis in a more advanced stage. 

At that time my animal experiments had been limited to 
the use of fifty-nine guinea pigs and five rabbits, for the very 
good reason that I had been unable to obtain more animals; 
and, while even a single positive result, if absolutely proved, 
would be sufficient to show that the experiment can be made 
■ successfully, the possibility of occasional failures in animals 
was still an open question. In order to determine possible 
failures, their causes and their frequency, my studies were 
continued and repeated on a larger scale. The scarcity of 
guinea pigs, which had existed in 1911, still being a hin¬ 
drance, 200 guinea pigs were, in the summer of 1912, im¬ 
ported for me from Germany by a New York dealer, and no 
difficulty was experienced with this lot. My criterion for 
the presence of a sufficient degree of immunity, by a quan¬ 
titative complement-fixation test, was met in every instance 
after a single full dose of vaccine in the human subject, and 
the sera which showed this standard never failed to destroy 
the virulence of 0.01 mg. of tubercle bacilli, as .shown in 
numerous animal experiments with proper controls. Neither 
had we any special difficulty in immunizing guinea pigs or 
rabbits, these animals reaching our standard in the comple¬ 
ment-fixation tests, as a rule, after ten to twelve doses of 
vaccine had been given, and the results of autopsies on the 
animals, together with those on their controls, justified me in 
again seeking confirmation of my results, by other observers, 
as I had done before and after my' first publication on the 
subject in 1912. 


5 


The winter before, I had applied to the Hygienic Labora- . 
tory in Washington, giving the director, Dr. Anderson, my 
reasons for my faith and asking him to take up the work 
with a view of checking my own before I would publish at 
all. He had then declined on account of lack of time. Soon 
after my publication I applied to him again. Dr. Anderson 
again declined, this time for lack of necessary assistants. 
When the Hygienic Laboratory took up the study of Dr. 
Friedmann’s preparation, I felt that I was being discrimin¬ 
ated against and again applied to Dr. Anderson, but was once 
more put off with the statement that my work was so well 
done and so ethically presented that it was not really neces¬ 
sary to repeat it, but that in any case the lack of appropria¬ 
tions for such work made it impossible for him to comply 
with my request. I therefore sought influence to bring about 
official action which, at my solicitation, led to 'the passage 
of a resolution in the U. S. Senate (No 89, May 26, 1913) 
which resolved 

“That the Secretary of the Treasury be, and he is hereby, requested 
to institute, through the Bureau of Public Health, an investigation of 
the practices and methods employed by Doctors Karl and Silvio von 
Ruck, of Asheville, North Carolina, in treating tuberculosis and in 
rendering persons immune from tuberculosis, and to report to the 
Senate, as soon as practicable, whether the vaccine used by the said 
Doctors von Ruck in attempting to render persons in health immune 
to tuberculosis is successful in immunizing those thus vaccinated.” 

Inasmuch as this Senate resolution provides for the investi¬ 
gation of our “practices and methods,” I naturally presumed 
that these were to be studied here in our sanatorium and re¬ 
search laboratory and, further, inasmuch as no attempt was 
made during several weeks after the arrival of the representa¬ 
tives of the Hygienic Laboratory to do any independent 
work, we had not anticipated any difficulties in the conduct 
of the investigation, on the mode and scope of which I*was 
not, however, consulted before their arrival or at any time 
thereafter; nor did they present to me any orders or cre¬ 
dentials from their superior officer. 

After a time, friction between the officers of the Hygienic 
Laboratory and the members of our laboratory staff appeared 
to have developed, of which I did not learn immediately, nor 
was I able to overcome it after having been informed of it 
by the chief of our laboratory, Dr. A. E. von Tobel. At 
that time also a much more reserved attitude became appar¬ 
ent on the part of the representatives of the Hygienic Labora¬ 
tory. Our invitation to participate in the practical work, by 
observing our method of the immunization of patients, was 
declined as being of no interest, and the only exception to 
this was their participation in the preliminary examinations 

6 


of a number of children who were to be vaccinated or treated, 
accordingly as the results of their examinations would deter¬ 
mine it. 

To our surprise the officers did not appear to have any 
interest whatever in our own determinations of the condition 
of these children, but made records without submitting them 
to us or suggesting a comparison with ours. As these exam¬ 
inations included certain biological tests of the blood sera, 
the blood specimens were taken by them and, to our still 
greater surprise, these specimens had disappeared from our 
laboratory on the following day. When, a few days later, 
animals were brought to the laboratory, as we believed, for 
the purpose of making bactericidal experiments with the sera 
of these children, before vaccination or treatment, our labora¬ 
tory chief requested an opportunity of describing these ani¬ 
mals for the purpose of subsequent identification whenever 
the results of these infections were to be determined. This 
the officers flatly refused, stating that they proposed to proceed 
entirely independently and that we could not know anything 
whatever of the results of the blood tests as determined by 
them, nor of their experiments. 

Both representatives of the Hygienic Laboratory having 
admitted to me that they had no previous experience in ex¬ 
perimental studies of tuberculosis and, there being evident 
at least an unfriendly attitude on their part and no apparent 
reason existing why we should permit these inexperienced 
men to become both judge and jury of our work and submit 
to being excluded by them from all knowledge of their pro¬ 
cedures, and this in our own laboratory, we informed the 
Director of the Hygienic Laboratory that we would not per¬ 
mit this mode of procedure. On his arrival in Asheville, a 
few days later, we made our position known to him during 
two conferences held for the purpose of finding a way by 
which the work could proceed. We objected to the proposed 
removal of the experimental studies to Washington, on ac¬ 
count of the lack of experience of the men entrusted with 
them; but an agreement was finally reached by Dr. Anderson 
agreeing that one of his men should remain with us until 
we were satisfied that he could work independently, after 
which the experiments should be conducted in Washington, 
without our supervision. 

During this interview we informed Dr. Anderson, among 
other matters, of our discovery of certain chemical changes* 
in the vaccine which had been prepared and finished in 1911, 
as compared with a more recent preparation in which some 
constituents were, however, still not fresh but dated from 

* See note, page 23. 


7 


1911. Dr. Anderson appeared much interested in the chem¬ 
ical analysis of the two preparations of the vaccine, and ex¬ 
tremely solicitous of obtaining a supply of the old and of 
the partially new preparation, which I agreed to deliver to 
him in the belief that he desired them for comparative chem¬ 
ical analysis. Recalling Dr. Anderson, after he had left us, 
and putting the question squarely to him, if it was not also 
his intention to make animal experiments with these samples^ 
he admitted this to be true. Although we delivered the vac¬ 
cine in spite of this admission, we accompanied it with a 
letter making the condition that, if used for experiments, 
we consented to such a use only conditionally, viz., that the 
study of these samples should not be official and that no 
report should be made or based on their action, a precaution 
which, under the circumstances, we felt to be prudent because 
we had, ourselves, not yet tried this vaccine and because it 
was not entirely fresh. The vaccine and the accompanying 
letter were' delivered to Dr. Anderson on his train, shortly 
before his departure, on Saturday, October 11, 1913, after 
he had repeated to me over the' telephone the assurance that 
one of his men, Dr. Stimson, should remain with us until we 
were satisfied of his ability to carry out the work. On Monday, 
October 13, I was informed by this officer that he had re¬ 
ceived orders by telegraph to discontinue his work with us 
and to return to Washington. 

This order naturally caused me to suspect that Dr. Ander¬ 
son’s agreement to leave Dr. Stimson in our laboratory was 
not made in good faith, but that it was made simply in order 
to conciliate us and to obtain possession of the samples of 
vaccine. On the day that Dr. Stimson left us, October 13, I 
wrote to Surgeon-General Rupert Blue, of the Public Health 
Service, and again discussed in detail my objections to the 
manner in which the investigation of my “ practices and 
methods in treating tuberculosis and in rendering persons 
immune from tuberculosis” had been commenced, at his or¬ 
ders. I pointed out to him that this investigation could not 
be conducted except by witnessing our practices and methods 
and that only then the propriety and desirability of addi¬ 
tional and independent studies in the Hygienic Laboratory 
could be considered. For the present, I told him that I was 
obliged to test the new preparation of the vaccine for its 
immunizing power and that, pending this examination, we 
desired that no animal experiments be undertaken by the 
Hygienic Laboratory and that no trials of the vaccine be 
made by it independently or otherwise for the treatment 
of tuberculous persons or for its prophylactic employment. 
I further made the condition that nothing that had been 

8 


done or was going to be done, independently of us or before 
we advised him that we were ready to demonstrate our 
methods and practices and our results when our methods 
and practices are applied by ourselves, as stated, should 
enter in the records of the investigation. 

To this protest, addressed to Surgeon-General Blue, no reply 
was received. I wrote to Dr. Anderson, on November 22, 
1913, asking him for the results of the chemical analysis 
of the samples of vaccine in question, if such an analysis 
had been made; if it had not been made, I requested him 
to return the vaccine to me so that I could have an examina¬ 
tion undertaken elsewhere. I told Dr. Anderson that I de¬ 
sired independent confirmation of the work done by our 
chemist and, as the amount of vaccine available was be¬ 
coming limited, I did not wish to sacrifice an additional lot. 

In a letter dated November 24, 1913, Dr. Anderson replied, 
saying that he was unable to return the vaccine, as it was 
being used in connection with certain experiments in the 
laboratory! Nothing further was heard from the Hygienic 
Laboratory until April 3, 1914, when we received a request 
for certain material (antigens), which we declined to supply. 

As I appeared to be powerless to protect myself against 
the arbitrary tactics of the Hygienic Laboratory and, under 
the circumstances, had reason to anticipate a biased and 
hostile report, I hoped to offset this by having the experiments 
made elsewhere by competent men of world-wide reputation, 
who would be able and willing to follow our methods and to 
conduct the experiments in a fair and impartial manner. 
Arrangements were accordingly made, first with Sir Almroth 
E. Wright, of London,, and with Privatdozent Dr. F. Wele- 
minsky of the German University at Prague. After having 
ben initiated in these laboratories, it was arranged to under¬ 
take like studies in the Pasteur Institute in Paris, in the 
Sero-Therapeutic Institute in Vienna (Professor Paltauf), 
in the Hygienic Institute in Danzig (Professor Petruschky) 
and, at the latter's suggestion, probably also in the Koch 
Institute in Berlin. We had previously arranged also for a 
study of the subject in this country and had purchased a 
large number of animals to be immunized in our laboratory 
and then to be shipped to their respective destinations for 
independent infection and for the subsequent report of their 
autopsy findings on comparison with reports on untreated 
animals, infected by the same observers, at the same times 
and places and in like manner. 

Having on hand a lot Of guinea pigs which we had thus 
treated for several months, these were tested and, to save 
time, the best of them, thirty-five in number, were selected 

9 


to be taken to Sir A. E. Wright’s laboratory, in London, by 
Dr. F. J. Clemenger of this city, who had offered his ser¬ 
vices in connection with the work abroad. Dr. Clemenger 
sailed for London on February 1 of this year and had placed 
the animals on board the steamer; but thirty of them were 
drowned in consequence of the bursting of a water pipe in 
the compartment where they had been placed before the 
steamer actually sailed; he, nevertheless, continued his jour¬ 
ney and arrived in London with the remaining five guinea 
pigs. 

During the preceding year we had found a considerable 
number of instances of spontaneous genuine tuberculosis 
among our experiment animals and an even greater number 
of cases of so-called pseudo-tuberculosis, which is caused by 
other bacteria, but sometimes so closely resembled the genuine 
type, following upon infection with Koch’s bacillus of tuber¬ 
culosis, that it could not be differentiated by ordinary inspec¬ 
tion at autopsy. The fact that these experiences came with 
increasing frequency caused us to watch for such cases more 
closely, because of the apparent failures in our experiments 
which would necessarily follow, should such already infected 
animals be used in the experimental studies under consideration. 
Dr. Clemenger, having also been cautioned before his de¬ 
parture that such animals were likely to be among his lot, 
made autopsies upon the drowned animals on board ship and 
found a number of them presenting the pseudo or spurious 
type. As he had but the five surviving animals on his ar¬ 
rival in London, these were killed and examined, and again 
pseudo-tuberculosis was found. The expected saving of time 
had thus not been accomplished. Upwards of 100 animals 
were then bought in London and their treatment with vac¬ 
cine was started about the middle of March. About forty 
of these animals died during their treatment and, in prac¬ 
tically all of them, pseudo-tuberculosis appeared to be the 
cause of death, the anatomical diagnosis being confirmed by 
Captain Douglas, the Associate Director of Sir A. E. Wright’s 
laboratory. 

I have before referred to our plan to treat a large number 
of animals with a view of having them subjected to infection 
by other observers in different medical centers in the United 
States. Four hundred guinea pigs were received for this 
purpose from a dealer in New York about October 1, 1913, 
and their treatment was started a few days after their ar¬ 
rival. Several of the animals had been found dead in the 
shipping boxes when they were received, and about thirty 
or more died within the first few days after receiving a 
small dose (1 to 3 mg.) of vaccine. Before another dose 

10 


was due, as many more had died and their autopsies showed 
genuine tuberculosis of internal organs; in many cases well- 
marked focal reactions were found surrounding the tubercu¬ 
lous lesions. The first localizations appeared frequently to 
be the intestines and mesenteric glands; in other cases the 
lungs and the bronchial glands. These lesions were found to 
be typical and to contain Koch’s bacillus of tuberculosis, 
verified by animal inoculation. An increased number of ani¬ 
mals died in the same manner during the administration of 
two more doses of vaccine, the autopsies giving like results 
in all. An inquiry of the dealer brought the reply that he 
had bought out the entire stock of a breeder in Pennsylvania 
who was obliged to go to California for his health, and that 
the animals in question had come from this stock. 

To meet a possible objection in this connection, I may point out that 
the vaccine could not have stood in relation to the tuberculosis found 
in these animals for the reason that it does not contain tubercle bacilli, 
either living or dead, and that the time between the administration of 
the vaccine and the death of the animals was far too short to justify 
such a conclusion. Death, in these cases, was due to hypersusceptibility 
to the administration of the specific antigen in large doses. 

Inasmuch as this lot of animals was not suitable for our 
purposes, a new lot of 425 and a smaller lot of fifty guinea 
pigs were obtained from other sources and, fearing that our 
pens were infected, these animals were kept on the farm of 
the Winyah Sanatorium and were cared for separately by 
men who never came in contact with the animals kept in the 
animal houses of the laboratory. A comparatively smaller 
number of deaths occurred in these animals also, after they 
were started on the vaccine treatment; their autopsies showed 
only small pneumonic areas in the lungs, not enough to ac¬ 
count for their deaths. The lesions were chiefiy limited to 
the extreme tips of one of the several lung lobes, with oc¬ 
casional implication of subjacent tissue, looking like con¬ 
tact extensions. As the deaths were comparatively few and 
most of the surviving animals appeared to gain in weight and 
to do well, these deaths were attributed to pneumonia caused 
by a short, Gram-negative bacillus which was not acidfast 
and which we could not identify more closely. The treatment 
of these guinea pigs was continued with small doses of vac¬ 
cine once a week until ten doses had been administered. When 
the animals were tested for specific antibodies, including the 
complement-fixation test, the latter was lacking quantitatively* 
and as a rule only a trace of antibodies was in evidence after 
repeating the test several times. Desiring to complete the 
immunization of these animals speedily, a decidedly increased 
dose (5 mg.) was administered, to which many animals suc¬ 
cumbed in the course of the following week; with rare ex- 
* See note, page 23. 


11 


ceptions all others had lost markedly in weight and continued 
to do so; numerous deaths occurred thereafter, the animals 
being found in a state of marasmus. The autopsy findings 
in all these animals were the same as in those of this lot 
which had died in the early part of treatment; i.e„, very 
small, sharply circumscribed pneumonic patches, usually the 
tips of one or more lobes; the bacteriological findings, in¬ 
cluding cultures from blood taken by-heart puncture, during 
life and after death, were the same; the isolated bacillus 
was Gram-negative, non-acidfast; growth on agar-glycerine 
was obtained in twenty-four to forty-eight hours. 

In the meantime numerous instances of genuine tubercu¬ 
losis had been found in animals never infected by us, and 
pseudo-types corresponding to that of rodents, described by 
A. Pfeiffer (cf. Centrdlbl. f. BaJct., 1890, VII, 219), and 
another pseudo-type caused by the Bacillus abortus Bang, 
with lesions like those described by Mohler and Traum (28th 
Annual Report, Bureau of Animal Industry for 1911, Wash¬ 
ington, 1913, p. 147) was found with increasing frequency 
in autopsies of animals that had been used for experiments 
in the course of our study. (The relation of the last-named 
organism was suggested to us by Dr. Adolph Eichhorn, of 
the Bureau of Animal Industry, and was amply confirmed on 
investigation.) 

Evidently we could not continue our experiments under such 
a state of affairs, and it was therefore determined to kill all 
animals on hand; to rebuild our animal houses, constructing 
them so that they could be readily disinfected, and then to 
start our work anew, hereafter placing the animals in indi¬ 
vidual cages. This was accomplished during the months of 
February and March of the present year. About 800 ani¬ 
mals, killed and autopsied, that had been under treatment 
before infection or had already been infected, almost without 
exception showed one of the three pseudo-types mentioned, 
often with genuine tuberculosis associated. Among' one lot 
of 118 1 ‘normal” animals, kept on hand to be used as re¬ 
quired, only two were apparently free from such an infection. 

At this time we were inclined to the belief- that the ob¬ 
served frequency of these pseudo and genuine infections was 
due to their spread in our houses and pens. We therefore 
took every precaution to prevent a recurrence, in the con¬ 
struction of the houses and in providing individual cages. 
In April, 1914, we were again ready for work and purchased 
one hundred guinea pigs direct from a breeder. These were 
used chiefly for the demonstration of the bactericidal power 
of immune sera taken after vaccination or treatment, and 
for the corresponding controls. 

12 


Aotbing further had been arranged concerning the govern¬ 
ment investigation, but we learned from a reliable source 
that, based upon the use of the vaccine obtained conditionally, 
the previous October, and on some few experiments started 
without my knowledge and consent in Asheville and con¬ 
cluded in Washington, a report unfavorable in nature was 
ready to be presented to the Senate. To prevent this mani¬ 
festly unjust procedure, I consented to a conference with the 
officers of the Public Health Service and with Assistant Sec¬ 
retary Newton of the Treasury Department in Washington, 
which occurred on April 22, 1914. Here I presented and read 
a written statement setting forth my objections to the mode 
of investigation adopted and, in the discussion which fol¬ 
lowed, it was proposed that, if I would supply vaccine, im¬ 
mune sera and immunized animals and other material to the 
Hygienic Laboratory and give them the same opportunity 
that I was giving or intended to give to the several labora¬ 
tories in Europe, no report would be made at this time. This 
I refused at first, stating frankly then and there that I did 
not trust the Director of the Hygienic Laboratory or the 
men detailed to do the work, and that I desired to postpone 
any further action on their part until I should know the re¬ 
sults of the work in Europe and until I had a more perfect 
preparation in the form of an entirely fresh vaccine, all 
of which could not be accomplished in less than six months. 

In the course of this conference Dr. Anderson himself 
stated that he had failed in his experiments, that his animals 
under treatment with vaccine had died of marasmus and that, 
in his opinion, the vaccine he had used had no value. 

It may be permissible in this connection to voice my astonishment 
that Dr. Anderson, of all men, should express such peculiar conclusions 
since he, together with Dr. Rosenau, was among the first to investigate 
the problem of hypersusceptibility, which is of such great importance 
in immunology and which fully explains his experiences with the ani¬ 
mals treated with the vaccine. Instead of basing upon the fact that 
these animals died of marasmus, the conclusions that the vaccine had 
no value, if he believes his own publications . to be correct and if 
he wishes to be consistent, he should rather have considered this fact 
as a proof of its specific nature (cf. Hyg. Lab. Bull. No. 36, p. 66, 
last paragraph; Bull. No. 45, p. 60, fifth paragraph) and should have 
taken it as a valid reason to grant to a preparation which could produce 
such symptoms a careful and unbiased investigation. 

I may add that, immediately on my return from Washington (April 
24), I wrote to Dr. Anderson asking him to supply me with copies 
of his records of the animal experiments upon which he based his 
unfavorable opinion. I took exception to one statement which he had 
made as incorrect, and pointed out the impossibility of certain matters 
alleged by him to be facts; finally I asked him to correct his state¬ 
ment, made in the presence of Secretary Newton, if he should find it 
to have been erroneous. To this letter I received no reply. 

13 


I was thus actually threatened with an adverse report 
based on work done with a sample of vaccine the use of 
which I had interdicted on its delivery and against the offi¬ 
cial use of which I had objected in my letter to Surgeon- 
General Blue of October 14. This was particularly serious, 
because it was at a time when I was about to go to Europe 
and could not well remain for the purpose of defending my¬ 
self, as would have become necessary if such a report had 
reached the Senate and had therefore become accessible to 
the public press. With such an adverse report, apparently 
reflecting unfavorably upon my work in my own country, I 
could not but fear difficulties in carrying to completion the 
studies contempated and arranged for in Europe, and the 
subject of prophylactic vaccination against tuberculosis would 
receive a set-back for many years to come if this adverse 
report, however unjustified it might be, were to be made now. 

While now I regret it deeply, I accepted Dr. Anderson's 
proposition, together with his assurance that the experiments 
should be made according to my written directions which I 
was to furnish; but also with the distinct provision incorpo¬ 
rated in a letter to me from Assistant Secretary Newton that, 
in case I were to supply a fresh vaccine which, in my opin¬ 
ion, was a more efficient preparation, in six months from 
April 24, the experimental work should be repeated and no 
report should be made to the Senate until the results from 
the use of the fresh vaccine were determined. 

While I still had my doubts and misgivings as to ever 
obtaining a fair and square deal from the Hygienic Labora¬ 
tory, I also felt sure of confirmation in Europe, for which 
there was now given me ample time, especially as my agree¬ 
ment provided a repetition of the experiments after October 
24, by which time I expected to have the new vaccine ready 
which was in course of preparation since November, 1913, 
and with which the experiments in Europe would be re¬ 
peated, if necessary. 

Once confirmed by superior and disinterested authorities, 
at the same time or before the Hygienic Laboratory could 
finish its work, it was also to be expected that the officers of 
the Public Health Service would abandon their evident skep¬ 
tical if not hostile attitude. The marasmus and other appar¬ 
ently unfavorable actions of the vaccine, claimed by Dr. 
Anderson, I had myself observed in hundreds of animals that 
had either spontaneously acquired genuine or pseudo-tubercu¬ 
losis, but never in animals which were free from these infec¬ 
tions. In the directions which I afterwards supplied, I called 
particular attention to the necessity of using only normal 
animals, i.e., such as were free from this kind of infections. 

14 


The gain in time would also enable me to publish my ex¬ 
periences in all directions since my first reports of 1912, and 
in the meanwhile it would afford an opportunity to study the 
causes and find the solutions of certain difficulties in comple¬ 
ment-fixation, with which I had been contending for some 
time. 

Leaving the subject of the government investigation, I 
may here interpose that the renewal of my animal experi¬ 
ments, in April of this year, was calculated to secure the 
same uniformity of success which I had experienced in the 
winter of 1911-12, in the crucial test of the bactericidal 
action of sera after vaccination.* 

Having agreed to prepare and to supply certain material 
to the Hygienic Laboratory, I was delayed in my departure 
for Europe and, althought this ddlay held up the work in 
London and Prague, it enabled me to close some of the pending 
Asheville experiments, the middle of May and the early part 
of Junei, and to verify once more the looked-for uniformity 
of success with the new lot of animals received on April 1, 
and this I was able to do without a single exception, all the 
controls showing generalized tuberculosis, whereas all the 
animals infected with tubercle bacilli to which immune serum 
had been added, were absolutely free from tuberculosis. 
The infected animals had behaved normally throughout the 
experiment, in like manner as I had formerly observed, and 
a lot under treatment with vaccine, some of them treated 
with large doses (10 to 20 mg.), progressed favorably, bear¬ 
ing these doses without harm and steadily gaining in weight. 
As soon as this normal behavior was evident, 100 more guinea 
pigs were ordered from the same breeder, further bactericidal 
experiments were undertaken upon them and more guinea pigs 
were put on treatment with the vaccine. 

The animals of this second lot were older, well grown and 
in apparently fine condition; but they did not behave as the 
first lot (which were! small, young animals) had done; they 
lost weight under treatment with vaccine and, when used for 
the bactericidal experiment, soon showed a marked difference 
in favor of the controls; those having received infections with 
tubercle bacilli after incubation with immune serum, by either 
not gaining or by losing weight progressively. A day or two 
before my departure for Europe I also had a number of the 
second lot killed, together with their controls, thirty or forty 
days after their infection—all had pseudo-tuberculosis as well 
as the genuine type; the experiment was a complete failure 
without exception, indeed the immune serum animals showed 
more marked lesions than did the controls. 

* See note, page 23. 


15 


I then ordered all the remaining animals to be killed and 
aut'opsie'd, and left instructions to kill a certain number of 
any lot that might be received on their arrival, and more or 
even all, if pseudo-tuberculosis were to be found. 

In the course of these experiences I had acquainted Dr. 
Anderson with our difficulty in obtaining normal animals, and 
had often and urgently requested him to supply us with some 
of his stock (which he had repeatedly assured me were entirely 
free from disease), at least in such number as he wished to 
use for experimental infection after they had been treated 
by us. On June 6, 1914, Dr. Anderson advised me that he 
would ship to me twelve guinea pigs on June 8, and on June 
11, as well as immediately before leaving Asheville, I wrote 
him that they had. not been received. To the two last-men¬ 
tioned letters he made no reply. 

About the time when the Washington pigs, from the Hy¬ 
gienic Laboratory, were due, we were likewise expecting a 
shipment of about fifty guinea pigs from Elyria, Ohio, and 
this shipment was delivered by the Southern Express Company 
on the 9th day of June, late at night, and was signed for by 
the night nurse of the Winyah Sanatorium. She called one 
of the laboratory assistants to take care of the animals, which 
were contained in three boxes. In one of them, two very 
small animals, apparently born in transit, were found dead. 
The rest were placed in individual cages. There were fifty 
animals and, as about fifty had been expected from Elyria, 
it was taken for granted that these animals were the ones 
expected from that source. One of them died a few days 
later of pneumonia and, according to instructions left by me, 
the probability of pseudo-tuberculosis among the rest of them 
was investigated by killing a small number, first, and more 
or all of them thereafter, if pseudo-tuberculosis were found 
frequently enough on autopsy. All of the remaining forty- 
nine guinea pigs were thus killed and in all of them, with 
two exceptions, was pseudo-tuberculosis found. Five or six 
other shipments from different breeders and dealers were 
received and examined in like manner during my absence, 
with like results, so that it appeared impossible to obtain 
normal guinea pigs and, as the sera from normal animals 
were believed to be necessary in the immunity tests by 
complement-fixation, and as we assumed that our difficulties 
with this test depended in all probability on the use of sera 
from diseased animals, all experimental work came to a 
standstill and remained in abeyance until my return from 
London. 

I was advised by letter of this state of affairs while in 
London, and again wrote from there to Dr. Anderson (July 

16 


6), begging him for a supply of animals from his normal 
stock to be sent to my laboratory in Asheville, as absolutely 
essential for our compliance with my undertaking to supply 
immunized guinea pigs and tested immune sera for the in¬ 
vestigation which he was conducting. To- this appeal I re¬ 
ceived a letter from Dr. Anderson, dated at Washington, July 
17, stating that he had shipped twelve guinea pigs as agreed 
in June, that he held the express receipt for the shipment and 
that he could spare us no more. His r&ply was promptly for¬ 
warded to Asheville with directions to determine the cause of 
the non-receipt of the pigs in question, ^hen it was found 
that one of the boxes delivered by the express company on 
June 9 had been shipped from Washington, the other two 
delivered at the same time having come from Elyria, Ohio. 
I received this information by letter, in New York, on my 
return from Europe, and Dr. Anderson was promptly informed 
personally by one of my assistants, who called on him at the 
Hygienic Laboratory in Washington. 

While this unfortunate accident could have been rectified 
had Dr. Anderson replied to my letters of June 11 and the 
following days, it supplied us, at the same time, with posi¬ 
tive information that pseudo-tuberculosis existed also in his 
stock of guinea pigs, inasmuch as of the total of fifty guinea 
pigs autopsied and examined, twelve must have been shipped 
from the Hygienic Laboratory. Granting that all three ani¬ 
mals found to be apparently free from it had been of the 
twelve received from Washington, there were still nine in 
which the disease was found, showing that Dr. Anderson was 
not aware of its presence in his stock. That this and our 
own experience is not unsual or exceptional, will presently 
appear from my personal observations in London. 

I have already stated that about one hundred guinea pigs 
were purchased in London, last March, for the purpose of 
immunization and later infection, and that during their treat¬ 
ment nearly one-half of them had died and had been found 
to have pseudo-tuberculosis. On my arrival in London some 
fifty pigs were still living and apparently in fine condition. 
To make sure that there was no pseudo-tuberculosis among 
them, eight were killed and in five of them this affection was 
found. Testing out the remainder for specific antibodies 
on three successive days, the test was more or less unsatis¬ 
factory, probably because we had no normal sera for comple¬ 
ment. The animals used for the supply of normal sera 
having been bled to death from the heart, under chloroform, 
and then autopsied, pseudo-tuberculosis was found in all of 
them. Four lots of guinea pigs were purchased from differ¬ 
ent sources, and pseudo-tuberculosis was present so uniformly 

17 


that there was no choice and their sera had to be used for 
complement fixation tests if the experiments were not to be 
completely abandoned. 

After consultation with Sir Almroth Wright and with Cap¬ 
tain Douglas, it was agreed to proceed with the experiments, 
since both men recognized not only the prevalence of pseudo¬ 
tuberculosis in guinea pigs in England as a common experi¬ 
ence, but also the detrimental effect of its presence on the 
experiments contemplated. It was hoped that some of the 
animals might have but slight infection of this kind or none 
at all. Complement-fixation tests were dispensed with by 
common consent in the bactericidal experiment and, instead, 
the sera of immunized persons were to be taken on three 
successive days, in the expectation that on one or more days 
they would protect insofar as the animals used for the test 
were normal.* Proceeding, then, upon this-plan, a new lot of 
guinea pigs was purchased and two of them being killed be¬ 
fore use and giving no evidence of pseudo-tuberculosis, it was 
hoped that this lot would turn out better and they were used 
for the bactericidal experiments and for all control experi¬ 
ments. At the completion of these infections, it was my 
purpose to go to Germany, but I was prevented by illness and, 
before my recovery, the war had broken out. I was exceed¬ 
ingly desirous of repeating the work in Germany, Austria 
and France, especially as I had assurance of normal animals 
„ in Prague, where fifty guinea pigs and twenty rabbits had been 
treated in the Hygienic Laboratory of the German University 
and were ready for infection. My telegrams and letters as 
to the prospects of carrying out my plans in spite of the war, 
remained unanswered and nothing remained for me but to re¬ 
turn home, a course urgently insisted upop, on account of my 
health, by Sir Almroth Wright and by the surgeon, Mr. Low, 
who attended me. 

Before I could leave England, several of the animals died 
within a week or ten days of their infection; they showed 
evidence of rapid loss of weight, which was considered to be 
a strong evidence of immunity by Sir Almroth Wright. In 
one of the animals nothing else but marasmus was found on 
autopsy; the others had pseudo-tuberculosis. Several success¬ 
ful terminations, but also as many failures, have been deter¬ 
mined upon animals that have died since my departure, cop¬ 
ies of the autopsy records having been forwarded to me by 
mail. From the description of the lesions recorded, it appears 
clearly that pseudo-tuberculosis was a factor in at least some 
of the failures. 


* See note, page 23. 


18 


Among the successful results are two guinea pigs treated 
with vaccine before infection, which- died without apparent 
cause. No tuberculosis was found on autopsy, while the cor¬ 
responding controls, which were killed for the purpose of 
comparative examination, showed generalized tuberculosis. A 
like result was shown in another guinea pig which had been 
infected with 0.01 mg. of tubercle bacilli, incubated with 
immune serum taken after a single dose of vaccine. This 
guinea pig showed no tuberculosis on autopsy,* whereas a 
control animal which died a few days later had generalized 
tuberculosis. 

On my return to Asheville, the state of my health prevented 
me from giving my personal attention to the resumption of 
the experimental studies beyond seeking a supply of normal 
animals. We had been so badly handicapped for nearly two 
years on account of pseudo-tuberculosis, and likewise in the 
routine work of the complement fixation test, that I was un¬ 
willing to go on in a manner under which we could never fore¬ 
tell with any degree of certainty what the results were likely 
to be. We had known for some time that animals suffering 
from pseudo-tuberculosis could as a rule not be successfully 
immunized with our vaccine. While most of them appeared 
to tolerate small doses, they failed to show evidences of im¬ 
munity after a course of treatment, which in our past ex¬ 
perience with normal animals had been ample and complete. 
When, after prolonged treatment, the desired . degree of im¬ 
munity had, in occasional instancs, been obtained, the animals 
often bore an infection so badly that death ensued from 
pseudo-tubercle bacillemia or toxemia, before the controls had 
time to develop marked evidences of disease. In bactericidal 
experiments with sera from immunized persons a like ex¬ 
perience was had; it was.remarkable in both methods for the 
demonstration of immunity that, though likewise suffering 
from pseudo-tuberculosis, the controls bore infection with 
tubercle bacillus emulsion alone, and also when such an 
emulsion had been exposed to the action of normal serum; 
in other words, the controls, although having pseudo-tubercu¬ 
losis, followed a normal course after infection, whereas such 
treated animals and those in which an immune serum had been 
used, did not, a marked toxemia developing which often 
killed quickly, but occasionally appeared to disappear, after 
which the animals recuperated as shown by a gain in weight. 
Yet, instances of failure to resist the infection completely 
were even then not uncommon. Before we had realized the 
relation of cause and effect, we had accepted all these cases 
as straight failures and, in the early part of 1913, had col- 

* See note, page 23. 


19 


lected some fifteen or twenty cases of this sort, although the 
lesions found in most pf them had appeared to be atypical 
and the infections had not followed the law of extension 
from the site of the infection. 

While our search for a certain supply of normal guinea pigs 
and rabbits has been cpntinued, we have concluded that we 
must breed our animals ourselves, under ideal conditions and 
precautions, and we have now a small stock of breeders which 
we received through the courtesy of the Bureau of Animal 
Industry. 

I further found on my return home that certain apparatus 
required for the preparation of vaccine had so frequently 
broken down that, for this reason, especially, the grinding of 
tubercle bacilli had not progressed as well as it should have 
done, and, being unable to import parts or new apparatus 
from Germany, we were obliged to have repairs made by local 
mechanics, which were often insufficient even for a single 
day’s running. 

I advised Dr. Anderson of all our difficulties and hindrances, 
as also of the status of the experiments in London, from which 
it appeared that the old vaccine was perhaps not so much at 
fault as I had feared when the spontaneous chemical changes 
were discovered in the fall of 1913, and I also expressed my 
fears that, owing to the difficulties with apparatus, we might 
not be able to finish an entirely fresh preparation of vaccine 
by the time the limit of six months from April 24 would 
expire. 

When, on October 2, a fire destroyed one of the buildings 
connected with the laboratory and the grinding apparatus 
was exposed to smoke and heat and was flooded with water, 
and when for purposes of safety it had to be torn out hur¬ 
riedly and removed, the prospect of finishing the new vaccine 
became still more problematical and, in view of the lack 
of normal animals and with our laboratory facilities sus¬ 
pended, I formally applied for an indefinite extension of time, 
in order to give me an opportunity to pursue the experimental 
studies quietly and unhampered by pressure of any sort, the 
investigation under the Senate resolution to be resumed when 
I would be in a position to supply everything essential in the 
way. of immunized animals, immune and normal sera of hu¬ 
man and animal origin, fresh vaccine and fresh antigens for 
complement-fixation tests, etc. This request was promptly 
refused, much to my astonishment; it was refused again in 
spite of the request of the United States Senator from whom 
the resolution for the investigation had originated. With 
much effort and the expenditure of extra time we nevertheless 
succeeded in finishing a small quantity (10 c.c.) of the new 

20 


vaccine, on October 23, which was mailed to Dr. Anderson 
at the Hygienic Laboratory the same afternoon; that is, 
twenty-four hours before the time limit expired, and the re¬ 
ceipt of which he acknowledged on October 26. We under¬ 
stand, however, that despite this, a report is to be pre¬ 
sented to the Senate on its reconvening in the early part 
of December and, while we have not the remotest intimation 
as to what this report will be, beyond the expression by Dr. 
Anderson at the time of rupture and again more recently, 
that the vaccine was not what I claimed it to be, I judge from 
our past experiences and from the attitude toward me more 
recently, that I must be prepared for an adverse report, an 
inference still further justified under _ the circumstances by 
the refusal to give us more time to comply with some requisi¬ 
tions utterly beyond our power to furnish at present, and 
by the repudiation of the agreement clearly stated in writ¬ 
ing that, in case we submitted a fresh preparation of vac¬ 
cine by October 24, the experiments should be repeated 
before a report could be made to the Senate. 

Prior to May, 1912, when I published my work on prophy¬ 
lactic immunization with the vaccine, it had not been applied 
clinically for the treatment of manifest tuberculous disease. 
On my return from Chicago, where the paper had been read 
on May 1, 1912, before the Chicago Medical Society, I gave 
the vaccine to the clinical department of the Winyah Sana¬ 
torium where it has since been used with remarkable success, 
especially notable being its rapid action in comparatively 
early stage cases, by which the time of treatment was reduced 
in many instances to one-third or one-half that formerly found 
necessary to obtain a result which justified the discharge of 
patients from our care. 

The vaccine was applied further for prophylactic purposes 
in children who gave evidences of previous exposure and in¬ 
fection in tuberculous families, with the same uniformity of 
physical improvement as witnessed in the cases reported by 
Dr. Julian of Thomasville, altogether upward of 2,000 chil¬ 
dren having been vaccinated, not counting those to whom the 
vaccine was administered by other physicians. 

Despite our difficulties in experimental tuberculosis in ani¬ 
mals, the practical work in prophylaxis and treatment of 
cases has been most gratifying in results. 

Since the summer of 1912, the vaccine has also been sup¬ 
plied to over 700 physicians; several have published then- 
experiences (aside from Dr. Julian, whose report has already 
been cited, papers were published by Drs. Frank Neall Robin¬ 
son, California State Journal of Medicine, March, 1914; Ros¬ 
well E. Flack, Charlotte Medical Journal, June, 1914; H. 

21 


Longstreet Taylor, St. Paul Medical Journal, July 1914), and 
numerous spontaneous reports have reached me by correspond¬ 
ence, confirming our personal observations. A collective in¬ 
quiry is now in progress, over six hundred question sheets 
having been sent out one week ago, to which, at this writing, 
about one hundred and fifty replies have been received, bear¬ 
ing witness to the great value of the vaccine for prophylactic 
as well as for therapeutic purposes. The results of this in¬ 
quiry will be tabulated and published in the immediate future, 
and the clinical results obtained in the Winyah Sanatorium 
will likewise be published in a forthcoming report on the 
completion of the work of the present year. 

This present pamphlet is written for the purpose of stating, 
in a general way, our experiences with the officers of the 
Public Health Service. Considering that we were not under 
indictment for fraud or misbehavior, unless possibly in the 
minds of our opponents, considering further that our consent 
to any investigation was absolutely essential, it being sub¬ 
ject to our free decision to refuse or to grant it, that we had 
a perfect right to a mode of conduct, of the investigation, 
in.a manner that we could know that our methods were fol¬ 
lowed and no errors were committed, considering finally that 
none of our protests were heeded, it must be clear to any 
fair-minded person that our practices and methods need not 
necessarily succeed in the hands of men who, although 
thoroughly competent in other phases of immunity studies, 
do this particular work independently of us for the first 
time, and that the practical results of our work, as con¬ 
templated by the text of the Senate resolution, should not 
have been ignored but should have been studied under our 
guidance as we offered that it should be done. To medical 
men it must appear equally clear that animal experiments 
are confirmatory or otherwise only when they tend to support 
the practical results, and that in all experimental studies many 
factors may enter which may obscure and even defeat their 
object, but that negative evidence constitutes no evidence at 
all whenever undoubted and well-proved successes can be 
shown against it. 

Such undoubted successes we have now at hand in the re¬ 
sults of the independent work of Sir A. E. Wright and his 
representatives, despite the difficulties which had to be met, 
and although the successes, of which we have been informed 
at this time, are but few in number, they will no doubt be 
materially increased when the experiments have been finished. 
Few as they are, however, they support and confirm the results 
which we ourselves had obtained when we had none but nor¬ 
mal animals and no technical difficulties to disturb us. 


22 


Could I have foreseen these difficulties, I should certainly 
not have sought this investigation until they were all elim¬ 
inated. Neither should I have consented to any independent 
work, to begin with, had I been consulted, and none was 
suggested or attempted by the representatives of the Hygienic 
Laboratory on their arrival. When it was insisted upon later, 
I promptly declined and stated my reasons at length and in 
writing. Having gone as far as I had, I did the best I could 
to patch up matters; but with a breach of faith, which is so 
evident now, on the part of the officers entrusted with the 
investigation, by even refusing to carry out that part of 
the agreement which I had stipulated for my protection, I 
can but fear that a final adverse report is intended to be made 
to the Senate. 

If, then, in this investigation, as it was conducted, the 
investigators have failed to confirm my claims, I hope to have 
my position fully stated when the report is presented to the 
Senate; I hope that the request will be made to appoint a 
new commission composed of physicians experienced in the 
study of tuberculosis immunity and in the practical part of 
the treatment of manifest tuberculosis, on which commission 
I shall have representation; that before this commission pro¬ 
ceeds independently in the investigation of our “practices 
and methods, ” we shall be accorded the right of demon¬ 
strating these practices and methods amply and fully in the 
clinical department of the Winyah Sanatorium and in its 
research laboratory in Asheville, in order to make sure that 
our practices and methods are fully understood and that 
sources of error will be eliminated on the part of the members 
of the commission; finally, that this commision shall under¬ 
take its labors only after I have given notice that I am 
ready and after I have had an opportunity of overcoming 
existing difficulties in regard to a supply of normal animals 
and other matters which have been obstacles to uniform suc¬ 
cess in the animal experiment. 

November, 1914. 


Note —During my trip to London, the European literature 
was not available to me because I had ordered it to be held 
in Berlin, having expected to use the journals in Germany. 
After my return from abroad, the accumulated files were not 
sent to me immediately and it was therefore only quite re¬ 
cently that I could take cognizance of a very important com¬ 
munication by Much and Leschke, in the Beitraege zur Blinik 


23 


der Tuberkulose (1914, XXXI, 335), which confirms me in 
many essential points. 

The observations and results of Much and Leschke, insofar 
as they are of interest in connection with my own researches, 
are briefly as follows: 

1. These authors have observed a deterioration in some of 
tlieir 11 partial antigens '’ which corresponds to the deteriora¬ 
tion, or, at least, the chemical changes that occurred in my 
vaccine. 

2. The authors found that an immunity to infection by 
tubercle bacilli exists only if antibodies to all constituents 
of the tubercle bacillus, to all partial antigens, can be demon¬ 
strated in the complement-fixation test. This confirms the 
criterion for a complete immunity which I had established in 
1911 and 1912, when I demanded that complement-fixation 
must be positive and complete with at least four antigens, 
if the immunized animals are to resist later infection. 

3. The authors succeeded in what I have called the bac¬ 
tericidal experiment; that is, in the infection of guinea pigs 
with virulent tubercle bacilli which had first been subjected 
to the action of serum from an immunized person. Their re¬ 
sults, in which these guinea pigs failed to acquire tubercu¬ 
losis, confirm me in my claim that in this manner the produc¬ 
tion of a complete immunity in a treated person can be dem¬ 
onstrated conclusively. 

This publication of Much and Leschke contains many other 
matters of interest, but the points which I have mentioned 
may suffice for my present purpose. 


CONFIRMATION IN LONDON. 

Cable just received from Sir Almroth Wright’s Laboratory 
in London advises complete confirmation in bactericidal and 
immunity experiment. 

December 2, 1914. Karl Von Ruck. 


24 





LIBRARY 















































